Membrane sphingolipids have been shown to be biologically active and exert numerous regulatory effects on cellular functions including modulating cell growth and differentiation. Ceramides, found in high concentrations within the cell membrane, are a family of lipid molecules composed of sphingosine and a fatty acid which function as structural elements, as well as signaling molecules. Studies have demonstrated important relationships between ceramide production and apoptosis in tumor cells and suggest that processes which enhance intracellular ceramide accumulation may provide in favorable proapoptotic effects during cancer chemotherapy (Bose et al. (1995) Cell 82:405-414; Mathias et al. (1998) Biochem. J. 335 (Pt 3): 465-480). Cell permeable short chain ceramides (C2- or C6-ceramide) have shown activity relevant to therapeutically treating cancer indications. For example, such ceramide forms have an anti-cancer effect on many cancer cell lines (reviewed in Radin (2003) Biochem. J. 371 (Pt 2): 243-256), including melanoma and soft tissue sarcoma (Auzenne et al. (1998) Melanoma Res. 8:227-239), Jurkat leukemia (Myrick et al. (1999) Leuk. Res. 23:569-578), and head and neck squamous cancer (Mehta et al. (2000) Cancer Chemother. Pharmacol. 46:85-92) cell lines. Ceramides C2, C6 and their analogues have also been shown to induce cell cycle arrest in a variety of tumor types (reviewed in Mathias et al. (1998) Biochem J. 335 (Pt 3): 465-480). Generation of endogenous ceramide has been shown to mediate apoptosis induced by a variety of anti-cancer drugs (reviewed in Mathias et al. (1998) Biochem. J. 335 (Pt 3): 465-480) including daunorubicin (Reddy et al. (2000) J. Immunol. 164:1355-1363), doxorubicin (Lucci et al. (1999) Cancer 86:300-311), ara-C (Strum et al. (1994) J. Biol. Chem. 269:15493-15497), suramin (Safavy et al. (2003) Bioconjug. Chem. 14:302-310), and paclitaxel (Charles et al. (2001) Cancer Chemother. Pharmacol. 47:444-450). Despite these observations, however, the molecular mechanisms underlying the therapeutically beneficial effects of ceramide, particularly cell permeable ceramides such as C6-ceramide, are unknown. This lack of understanding has hindered the development of compositions and methods containing ceramide (e.g., C6-ceramide) in combination with other agents that enhance the specific anti-cancer pathways affected by ceramide and/or overcome the pro-survival side effects of many anti-cancer therapeutics currently used in the clinic. Accordingly, there is a great need in the art to better understand the molecular mechanisms underlying the anti-cancer effect of ceramide and its derivatives.